ArticleCell2016
A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling.
Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 143 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase III MultiCenter Randomized Controlled Study to Assess Efficacy and Safety of ON 01910.Na 72-Hr Continuous IV Infusion in MDS Patients With Excess Blasts Relapsing After or Refractory to or Intolerant to Azacitidine or Decitabine
A Phase III, International, Randomized, Controlled Study of Rigosertib Versus Physician's Choice of Treatment in Patients With Myelodysplastic Syndrome After Failure of a Hypomethylating Agent
Who cites it
143 citing papers in PubMed, 277 citations in OpenAlex.
- Rigosertib Reverses Hypertrophic Cardiomyopathy in Noonan Syndrome.Circulation · 2026Article
- Small-molecule RAS/RAF inhibitors target RAS-driven cancers via allosteric RAF disruption.Nature communications · 2026Article
- GDP-Loaded K-Ras Transiently Binds to Effector B-Raf RBD, Mirroring the Structure of the Active GTP-Loaded Complex.Journal of the American Chemical Society · 2026Article
- Clinico-genomic characterization of RAS-mutant acute myeloid leukemia.Annals of hematology · 2026Article
- Atorvastatin negatively regulates MAPK pathway in vitro to inhibit proliferation, migration, and invasion of hepatocellular carcinoma cells.Scientific reports · 2025Article
- Targeting Kinase Suppressor of Ras 1 (KSR1) for Cancer Therapy.Pharmaceutics · 2025Review
- A machine learning-based analysis method for small molecule high content screening of three-dimensional cancer spheroid morphology.Molecular pharmacology · 2025Article
- Unlocking the therapeutic potential of rigosertib as a selective therapy for ovarian cancer.Cell reports. Medicine · 2025Article
- The complex journey of targeting RAS in oncology.BMC cancer · 2025Review
- CETSA-MS unveils novel targets engaged by rigosertib to promote anti-tumor activity and inflammatory responses.iScience · 2025Article
- Differential scanning fluorimetry followed by microscale thermophoresis and/or isothermal titration calorimetry as an efficient tool for ligand screening.Biophysical reviews · 2025Review
- Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia.Molecular cancer therapeutics · 2025Review
- Motif-guided identification of KRAS-interacting proteins.BMC biology · 2024Article
- Elraglusib Induces Cytotoxicity via Direct Microtubule Destabilization Independently of GSK3 Inhibition.Cancer research communications · 2024Article
- Towards Targeting Endothelial Rap1B to Overcome Vascular Immunosuppression in Cancer.International journal of molecular sciences · 2024Review
- Functional and structural insights into RAS effector proteins.Molecular cell · 2024Review
- Review
- Drug screening in human physiologic medium identifies uric acid as an inhibitor of rigosertib efficacy.JCI insight · 2024Article
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- Single-cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy.Cancer research communications · 2024Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Oncogenic activation of RAS genes via point mutations occurs in 20%-30% of human cancers. The development of effective RAS inhibitors has been challenging, necessitating new approaches to inhibit this oncogenic protein. Functional studies have shown that the switch region of RAS interacts with a large number of effector proteins containing a common RAS-binding domain (RBD). Because RBD-mediated interactions are essential for RAS signaling, blocking RBD association with small molecules constitutes an attractive therapeutic approach. Here, we present evidence that rigosertib, a styryl-benzyl sulfone, acts as a RAS-mimetic and interacts with the RBDs of RAF kinases, resulting in their inability to bind to RAS, disruption of RAF activation, and inhibition of the RAS-RAF-MEK pathway. We also find that ribosertib binds to the RBDs of Ral-GDS and PI3Ks. These results suggest that targeting of RBDs across multiple signaling pathways by rigosertib may represent an effective strategy for inactivation of RAS signaling.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.